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Updated: Oct 5, 2025
Spinal Cord Neurons Isolation and Culture from Neonatal Mice
Published on: July 11, 2017
Neuroprotective effect of aldose reductase knockout in a mouse model of spinal cord injury involves NF-κB pathway
Fu-Xin Han1, Rui Zhang2, Xin-Xing Yang3
1Department of Neurosurgery, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, 710004, P. R. China.
Abstract:
The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Activated microglia/macrophages have either detrimental or beneficial effects on neural regeneration based on their functional polarized M1/M2 subsets. Aldose reductase (AR) has recently been shown to be a key component of the innate immune response. However, the mechanisms involved in AR and innate immune response remain unclear. In this study, wild-type (WT) or AR-deficiency (KO) mice were subjected to SCI by a spinal crush injury model. AR KO mice showed better locomotor recovery and smaller injury lesion areas after spinal cord crushing compared with WT mice. Here, we first demonstrated that AR deficiency repressed the expression level of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS) in vitro via the activation of autophagy. AR deficiency caused 4-hydroxy-2-(E)-nonenal (4-HNE) accumulation in LPS-induced macrophages. We also found that exogenous addition of low concentrations of 4-HNE in LPS-induced macrophages had the effect of promoting further activation of NF-κB pathway, whereas high concentrations of 4-HNE had inhibitory effects. Together, these results indicated that autophagy as a mechanism underlying AR and 4-HNE in LPS-induced macrophages.
Insights
Aldose reductase (AR) deficiency improves recovery after spinal cord injury (SCI) by modulating macrophage function and reducing inflammation. This study reveals AR
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Spinal cord injury (SCI) triggers inflammation involving microglia and macrophages.
- Macrophage polarization (M1/M2) influences neural regeneration outcomes.
- Aldose reductase (AR) is implicated in innate immunity, but its role in SCI is unclear.
Purpose of the Study:
- To investigate the role of aldose reductase (AR) in the inflammatory response following spinal cord injury (SCI).
- To elucidate the mechanisms by which AR influences macrophage function and neural recovery post-SCI.
Main Methods:
- Spinal cord crush injury model in wild-type (WT) and AR-deficient (KO) mice.
- In vitro studies using lipopolysaccharide (LPS)-induced macrophages to assess AR's effect on inducible nitric oxide synthase (iNOS) and autophagy.
- Analysis of 4-hydroxy-2-(E)-nonenal (4-HNE) accumulation and its impact on NF-κB pathway activation.
Main Results:
- AR KO mice exhibited improved locomotor recovery and reduced lesion size compared to WT mice after SCI.
- AR deficiency suppressed LPS-induced iNOS expression in macrophages via autophagy activation.
- AR deficiency led to 4-HNE accumulation; low 4-HNE promoted NF-κB activation, while high concentrations inhibited it.
Conclusions:
- Aldose reductase plays a detrimental role in spinal cord injury recovery.
- Autophagy mediates the effects of AR and 4-HNE in macrophages, influencing the inflammatory response.
- Targeting AR may offer a therapeutic strategy for enhancing recovery after SCI.
